Scintilla – a flash, a spark, an iota. Shorthand for creativity and an indicator of inventiveness under Australian law.

Wednesday, November 23, 2016

Leave the Interference to the Ribonucleic Acid: iRNA Patent Finally Gets There

By Lev Gutkin, Lawyer

Talk about perseverance! Four adverse examination reports didn’t stop Arrowhead Research Corporation from pursuing its patent application, and its efforts have finally paid off, after seeing off the final objection, that its patented invention was not a 'manner of manufacture'. Arrowhead is now the proud owner of an interference RNA patent.

The patent application relates to the process of RNA interference and its use for attenuation of unwanted or pathological protein expression, specifically that of spleen tyrosine kinase (Syk). The registrar's most recent ground for rejecting the application was that the patent was not for a 'method of manufacture' because it claimed double stranded RNA molecules. The 'method of manufacture' objection stemmed from the decision of the High Court in D'Arcy v Myriad Genetics Inc, discussed in a previous post. The majority decision in D'Arcy established that naturally occurring DNA sequences, even if isolated from the rest of the cellular contents, failed to satisfy the 'manner of manufacture' requirement as they are in truth better characterised as 'information'.

DNA resides within human cells in double stranded form, and a type of single stranded RNA, mRNA, is made using DNA as a template. mRNA is then used as the 'instructions' for the synthesis of a protein. Generally speaking, more of a particular mRNA in a cell means more of the encoded protein is made. However, human cells have an inbuilt mechanism, where, if double stranded RNA is introduced into the cell, it is processed and split into the constitutive strands. One of these strands associates with an enzymatic complex that degrades complementary mRNA strands, resulting in less overall mRNA and therefore less protein. Where those proteins are the cause of an illness, the introduction of double stranded RNA in this manner can have a therapeutic effect. This mechanism has generated a great deal of scientific interest due to its potential for creating highly targeted medical treatments.

The Cure for Lack of Manners

'Manner of manufacture' was raised as an issue in the last three of the four examination reports. The issue was that a necessary component of the claimed double stranded RNA molecules was a sequence of nucleotides which corresponded to the sequence in the mRNA being targeted, and so would also need to correspond to the sequence in the original DNA. In the fourth report, Examiner Christina van Broekhoven concluded that 'the utility lies in the sequence itself, and the substance of the product is information', so accordingly the manner of manufacture requirement was not met.

Arrowhead requested a written hearing, and provided its submissions in June, putting forth a number of arguments. It argued that the characterisation made of its invention was incorrect, instead what was claimed was a pharmaceutical substance (basically, a drug) of the nature discussed by the High Court in Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd, which referred to the way this term is defined in the Patents Act. Arrowhead also put forth the argument that to be characterised as 'information' per the reasoning of the High Court in D'Arcy, the sequence in the claimed molecule needed to be 'something resulting in the propagation of cause and effect within a biologic system', for example a sequence coding for a particular protein, or affecting the susceptibility of an individual to a disease; the mere inclusion of nucleotides would not turn the molecule into the nature of 'information'.

Arrowhead emphasised that the double stranded RNA molecules claimed in the patent differed from known naturally occurring molecules, as DNA has a different chemical structure (deoxyribose instead of ribose in the backbone, and thymine instead of uracil as one of the nucleic acids), and the naturally occurring mRNA sequences are single stranded.

Delegate Calanni sided with Arrowhead. She considered that the double stranded structure of the claimed molecules is at least equal in significance to how the invention operates (since putting single stranded RNA into a cell won't result in the desired attenuation). The informational, structural and chemical characteristics of the claimed molecules were each considered an essential element the invention, so the preferable view was that the substance of the invention is that of a pharmaceutical composition. The Delegate's decision appears to also have been influenced by the fact that the claimed molecules could be used as a medical treatment, similarly to more conventional drugs, and so arguably belong in the same category.

Prove It!

In its submissions, Arrowhead argued that there is no requirement for the applicant to show that what is claimed does not exist in nature; instead the starting point is that the invention is patentable unless it is shown otherwise. The post Raising the Bar provisions of the Patents Act applied to the examination, and s49 now provides that acceptance of a standard patent request is only required where the Commissioner is satisfied, on the balance of probabilities, that requirements such as manner of manufacture are met. Arguing that the onus should rest on the Examiner to prove that a substance is not naturally occurring seems a bold move. However, it is understandable why such an approach would be taken, given that a definitive statement by an applicant that the claimed molecule does not exist in nature may expose the patent to revocation on the ground of false suggestion, if evidence to the contrary later arises.

Take Away

Subject to a contrary decision by a higher authority, it appears that patents for double stranded RNA usable for RNA interference can be obtained in Australia: likely a relief for many researchers working in the field. The precise delineation between what is merely unpatentable genetic information and what is a patentable pharmaceutical substance is likely to be matter of debate for years to come. This decision serves as a reminder that the majority judgment in D'Arcy said that the subject matter of the claims being considered by them in that case lay 'at the boundaries of the concept of "manner of manufacture"', and there were a number of factors that together led to their decision. Proving novel structural and chemical elements to a claimed molecule, or a direct therapeutic application, may be enough to tip the scales in the patentee's favour. For those not faint of heart, attempts to patent new molecules born of future scientific ingenuity featuring nucleotide sequences continue to be a worthy endeavour.

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